It is of great significance to ability to obtain new natural products with diverse activities through the study of soil microorganisms. However, less than 1% of the total soil microorganisms can be cultured under laboratory conditions, thus limiting the discovery of new compounds. Metagenomics, by which the genomic DNA of soil microorganisms can be extracted and expressed in heterologous hosts, provides a new approach for the functional study of soil microorganisms. Natural halides have good bioactivities, including antibacterial and antitumor activities. Halogenases play an important role in biosynthesis, and introducing bioactivities of halogenated compounds. To investigate the potential of halogenated compounds production from soil microorganisms, a soil metagenomic library was screened by PCR for clones harboring reduced flavin adenine dinucleotide (FADH2) - dependent halogenase genes. Sixty-five positive clones were identified from the library, and the amino acid sequences of halogenase genes within the positive clones were analyzed. Phylogenetic analyses revealed that more than 85% of these genes were separated from known halogenases to form new clades in the phylogenetic tree; moreover the soil-derived halogenases showed high diversity. By further biosynthetic gene analysis of the positive clones, a new type I polyketide biosynthetic gene sequence was identified, which is probably related to the biosynthesis of the halogenated type I polyketide. In conclusion, novel and diverse halogenase genes were identified on sixty-five metagenomic clones using a sequence-driven metagenomic approach, laying a foundation for the further discovery of novel natural halides biosynthetic gene clusters and halides.